液相色谱-质谱法检测甲磺酸沙非胺中基因毒性杂质

    Determination of Genotoxic Impurities in Safinamide Mesylate by LC/MS

    • 摘要: 甲磺酸沙非胺主要用于治疗帕金森病,建立了甲磺酸沙非胺中基因毒性杂质((S)-4-(((1-氨基-1-氧丙烷-2-甲基)氨基)甲基)苯甲磺酸酯)的液相色谱-质谱联用检测方法。样品溶于甲醇,经YMC-Triart C18(4.6 mm×100 mm, 3μm)分离,0.1 %甲酸水和0.1 %甲酸甲醇梯度洗脱,采用多反应监控(MRM)模式正离子扫描进行定量检测。该方法具有较好的专属性,目标化合物在1.53~30.54 ng/mL的浓度范围内线性关系良好(R2>0.99);检出限为0.76 mg/kg,定量限为1.53 mg/kg;加标回收率为98.5%~99.90 %,RSD为0.83%~2.10%。该方法灵敏度高,准确可靠,可应用于甲磺酸沙非胺的质量监控。

       

      Abstract: Safinamide mesylate is mainly used in the treatment of Parkinson's disease. A liquid chromatography-mass spectrometry (LC-MS) method was developed for the determination of genotoxic impurities ((S)-4-((1-amino-1-oxopropane-2-methyl)amino)methyl)benzoate) in safinamide mesylate. The sample was dissolved in methanol, separated by YMC-Triart C18 column (4.6mm×100 mm, 3μm), eluted with 0.1 % formic acid in water and 0.1 % formic acid in methanol gradient, and quantified by positive ion scanning in multiple reaction monitoring (MRM) mode. The method has good specificity, and the target compound has a good linear relationship in the concentration range of 1.53-30.54 ng/mL. Standard recovery rate was 98.5%~99.90% with relative standard deviations of 0.83%~2.10%. The linear response range was between 1.53~30.54 ng/mL (R2 >0.99). The results showed that the method was sensitive, accurate, reliable and suitable for screening of genotoxic impurities ((S) - 4 - ((1-amino-1-oxopropane- 2-methyl) amino) methyl) in safinamide mesylate.

       

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